This is a monthly digest of interesting information that is being added to Allergy Advisor. While we add a great deal of information every month, here we highlight some of the more interesting articles.
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Development of sesame tolerance and cosensitization of sesame allergy with peanut and tree nut allergy in children.

Anaphylaxis caused by honey: a case report.

Conjunctival provocation test in diagnosis of peanut allergy in children.

Hypothesis: may e-cigarette smoking boost the allergic epidemic?
The hypothesis that e-cigarette increases S. aureus colonisation and then induces sensitization is important to consider since S. aureus colonisation is needed for the development of an IgE immune response that is often associated with a polyclonal IgE response, allergic symptoms of the upper and lower airways including allergic rhinitis, severe asthma and/or chronic rhinosinusitis with nasal polyposis. Although currently there is no confirmation that e-cigarette smoking may induce allergic diseases, there is sufficient background to seriously consider this hypothesis and to test it in appropriate cross-sectional and longitudinal epidemiologic studies.

Galactose-alpha-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity?
First described as the target of IgE in individuals suffering immediate hypersensitivity reactions to the novel anti-EGF monoclonal antibody cetuximab, it is now clear that alpha-gal sensitization is associated with mammalian meat allergy as well as reactions to other mammalian products. Unlike traditional IgE-mediated food allergies, reactions to alpha-gal often do not manifest until several hours following an exposure, although co-factors can influence the presentation. Multiple pieces of evidence, including recent work with a mouse model, point to the fact that sensitization is mediated by exposure to certain hard ticks and increasingly we are aware of its globally widespread impact. The oligosaccharide alpha-gal represents a novel allergen with several unusual clinical features. It has been recognized now on multiple continents and its clinical presentation can be quite variable. Moreover, efforts to delineate the mechanisms leading to alpha-gal sensitization may have ramifications for our broader understanding of type 2 immunity.

An overview of nonsteroidal antiinflammatory drug reactions.
Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the most commonly used drugs worldwide. They account for a large number of adverse drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing. Distinguishing between a predicted side effect of a drug and a potentially life-threatening hypersensitivity reaction is essential to manage the affected patient. However, most clinicians find it difficult to diagnose these types of reactions despite published classification schemes. In this overview, we provide an in-depth review of NSAID classification, types of NSAID reactions, diagnostic tactics, and management strategies to provide the reader with a greater understanding of NSAID-induced reactions

The Role of Fungi in Atopic Dermatitis.
There is little doubt that Malassezia spp plays a role in atopic dermatitis because it may interact with the local skin immune responses and barrier function, and sensitization against this skin-colonizing yeast can correlate with disease activity. Also, antifungal therapy shows beneficial effects in some patients. However, the pathogenetic mechanism and mutual interaction between Malassezia spp and atopic dermatitis still remain partly unclear and need further investigation.

Cutaneous manifestation of food allergy.
Hypersensitivity reactions to foods can have diverse and highly variable manifestations. Cutaneous reactions, such as acute urticaria and angioedema, are among the most common manifestations of food allergy. However, cutaneous manifestations of food allergy encompass more than just IgE-mediated processes and include atopic dermatitis, contact dermatitis, and even dermatitis herpetiformis. These cutaneous manifestations provide an opportunity to better understand the diversity of adverse immunologic responses to food and the interconnected pathways that produce them

Bariatric Surgery: A Novel Risk Factor for Food Allergy?
In this case report, we describe a birch pollen-allergic patient in whom a Fobi pouch gastric bypass was associated with the transition from a mild, localized, birch pollen-related oral allergy syndrome to more severe, generalized allergic reactions to peach.

A case of anaphylaxis to patent blue
In medicine, patent blue violet (PBV) is utilized for staining lymphatic vessels in sentinel lymph node (SLN) surgery. Moreover, PBV (also called E131 ) is used as food additive. We report on a 51-year-old non-atopic female with early breast cancer, who was scheduled for SLN excision and experienced an intra-operative anaphylactic reaction. In diagnostics the skin prick test (SPT) was positive to PBV. Hypersensitivity reactions to PBV can arise after the first exposure in surgery as sensitization may arise from either PBV (E131) in foods (i.e. in sweets or blue curacao) or from other structurally closely related triarylmethane dyes in objects of everyday life like textiles, detergents, paints, cold remedies and cosmetics. This article supports the necessity of an increased awareness of the possibility of anaphylactic reactions to PBV during SLN surgery, even if the patient never had contact to PBV before.

Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens during the first 2 decades of life.
The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (>/=0.35 kUA/L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma

Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in peanut allergic children.
Eliciting doses (ED) of allergenic foods can be defined by the distribution of threshold doses for individuals within a specific population. ED05 is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED05 for peanut (PN) is 1.5 mg of peanut protein (6 mg whole peanut). This study sought to validate the predicted peanut ED05 (1.5 mg) with a novel single dose challenge. Consecutive eligible peanut allergic children in 3 centres were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used to identify ED05 single dose reactors. 518 children (mean age 6.8 years) were eligible. 378 children (206 male) completed the study. Almost half the group reported ignoring precautionary allergen labelling. 245 (65%) experienced no reaction to the single dose of peanut. 67 (18%) reported a subjective reaction without objective findings. 58 (15%) experienced signs of a mild and transient nature that did not meet the pre-determined criteria. Only 8 subjects (2.1%, 95% CI 0.6%-3.4%) met the pre-determined criteria for an objective and likely related event. No child experienced more than a mild reaction, 4 of the 8 received oral antihistamines only and none received epinephrine. Food allergy related quality of life improved from baseline to 1 month post challenge regardless of outcome. Peanut SPT, peanut and Ara h 2 spIgE levels were not associated with objective reactivity to PN ED05.

Validation of recipes for double-blind placebo-controlled challenges with milk, egg white, and hazelnut.
We developed 3 recipes for use in DBPCFC with milk, egg white, and hazelnut and used the triangle test to validate them in a 2-phase study in which 197 volunteers participated. We used sensory testing to validate milk, egg white, and hazelnut recipes for use in DBPCFC. The validated recipes are easy to prepare in a clinical setting, provide the equivalent of 1 serving dose, and were liked by most participants.

Key issues in Hymenoptera venom allergy: an update.
In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis

Phenotypical characterization of peanut allergic children with differences in cross-allergy to tree nuts and other legumes.
The three phenotypes highlighted by the present study could be useful to identify children with high risk of cross-allergic reaction to TNs and legumes early after PA diagnosis.

Non-IgE-mediated gastrointestinal food allergies in children.
Non-IgE-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) including food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE), and food protein-induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under-diagnosed. Non-IgE-GI-FA have a favorable prognosis, with majority resolving by age 3-5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants.

Systemic reaction after performing a food prick-to-prick test
A 47-year old woman with a history of persistent allergic rhinitis, sensitized to the pollen of grasses, olive and salsola; was assessed for anaphylaxis triggered by the consumption of avocado, cantaloupe, carrots and watermelon. Minutes after skin prick test with standardized extract and skin prick with fresh foods, she developed dyspnea, pruritus, erythema, dizziness and sibilance. Although skin tests are safe, the risk of hypersensitivity and anaphylactic reactions should not be ruled out, especially in susceptible patients.

Cow's milk allergy: towards an update of DRACMA guidelines.
In 2010, the diagnosis and treatment of IgE-mediated CMA were systematized in a GRADE guideline. After 6 years, the state of the knowledge in diagnosis and treatment of CMA has largely evolved. We summarize here the main advances, and exemplify indicating some specific points: studies aimed at better knowledge of the effects of breastfeeding and the production of new special formulae intended for the treatment of CMA. The literature was searched. The authors drew on their collective clinical experience to restrict retrieved studies to those of relevance to a pediatric allergy practice.

Conclusions: Evidence-based diagnostic criteria should be identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely assessed in the last six years. In the substitute choice, clinicians should be aware of recent studies that can modify the interpretation of the current recommendations. New systematic reviews and metanalyses are needed to confirm or modify the current DRACMA recommendations

Baked milk tolerant patient: Is there any special feature?
Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. A cross-sectional study was conducted. Patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for alpha-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM. Therefore baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and alpha-lactalbumin.

Allergic respiratory disease: different allergens, different symptoms.
Different types of aeroallergens and specific sensitization profiles are associated with different allergic clinical pictures (rhinitis with/without asthma), different clinical symptoms and severity. This could have implications to predict later clinical course and to select appropriate management approaches.

Characterization of the T-cell response to Dau c 1, the Bet v 1-homolog in carrot.
Dau c 1 displays several characteristics of sensitizing allergens, namely a major T-cell-activating region, low susceptibility to endolysosomal degradation, and induction of a Bet v 1-independent T-cell response. These cellular insights confirm that the major carrot allergen has a special status among Bet v 1-related food allergens.

LEAPing Through the looking glass: secondary analysis of the effect of skin test size and age of introduction on peanut tolerance after early peanut Introduction.
In the Learning Early About Peanut Allergy (LEAP) study, early peanut introduction in high-risk 4-11 month olds was associated with a significantly decreased risk of developing peanut allergy. However, the influence. Secondary analysis was conducted on the publically available LEAP dataset, exploring relationships between peanut tolerance, baseline peanut/egg sensitization, eczema severity/duration, age of introduction, gender, and race. Increasing peanut wheal size predicted peanut tolerance only in the avoidance arm. Peanut introduction between 6-11 months of age was associated with the highest rates of peanut tolerance, questioning the 'urgency' of introduction before 6 months.

A Korean multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in children and adolescents.
Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Prediction of clinical peanut allergy status among children in Hamilton, Ontario
The gold standard for diagnosing clinical peanut allergy is the oral food challenge, but this method is time-consuming and can cause severe allergic reactions. It would therefore be beneficial to develop a tool for predicting clinical peanut allergy in peanut-sensitized individuals whose peanut allergy status is unknown so as to better determine who requires an oral food challenge for diagnosis. Two separate studies were conducted. Peanut skin prick test wheal size was the best predictor of clinical peanut allergy in both study cohorts. For every 1 mm increase in wheal size, the odds ratio of an individual having clinical peanut allergy was 2.36 in our first cohort and 4.85 in our second cohort. No other variable approached the predictive power of wheal size.

The impact of age on Pru p 3 IgE production in Italy.
This study aimed to to test the hypothesis about the differences of Pru p 3 sensitization across Italy, mainly concerning the impact of age. The current study was retrospective and multicentre, involving 2 labs in Northern Italy (709 subjects), 1 in Genoa (1,040 subjects), and 1 in Southern Italy (2,188 subjects). All of them referred to labs for IgE testing because of suspected food allergy. Serum IgE to Pru p 3 was assessed in all subjects. The study concludes that Pru p 3 sensitization and production are closely age-dependent phenomena.

International Consensus Guidelines for the Diagnosis and Management of Food Protein-Induced Enterocolitis Syndrome: Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma, and Immunology.